Aerosol drug therapy from a liquid solution or suspension containing active ingredients by a jet nebulizer or an ultrasonic nebulizer has been used in hospitals, outpatient clinics and at home. A jet nebulizer uses a high speed air jet, created by compressed air supplied to one or more nozzles, to break a stream of fluid into primary droplets. An ultrasonic nebulizer uses ultrasonic energy to break up a liquid film. The jet or ultrasonic nebulizer is incorporated into an inhaler used to administer medication to the pulmonary system of a patient.
The primary droplets of jet nebulizers have a mean size of between 15 and 500 micrometers, which is reduced to about 1 to 10 micrometers by directing the droplets to impaction baffles. Between 93% and 99% of the generated primary droplets are caught by the baffle system and are returned to the reservoir for continued generation. The droplet size from ultrasonic nebulizers is usually between 5 and 10 micrometers. Nebulization is a dynamic process with continuous changes in total output and droplet size. In continued operation, the solution cools down from room temperature to about 11.degree. C. to 15.degree. C. due to water droplet evaporation. Consequently, concentrations in both the solution and the droplets increase with time. The droplet particle size is sensitive to the ambient temperature, relative humidity and flow rate. These parameters, in turn, affect the evaporation and condensation of water droplets. Loss of droplets in the transport system between the nebulizer and the mouth can be high, depending on the droplet size and the design of the gas flow structure.
It is well known that most commercially available aerosol generating devices do not produce monosize droplets, but a spectrum of polysize droplets. Even the best nebulizers do not always produce a monosize dispersion of liquid droplets. This is especially true in conditions where the orifice used for dropletization becomes contaminated by perimeter surface deposits, such as salts, oils, etc. or by macro particle blockage, such as dirt, fiber etc. All aerosol devices fail when the dropletization nozzle clogs and when the droplet dispersion pneumatics become inadequate.
Researchers are investigating the benefits of a portable, handheld drug delivery system to augment and replace the current CFC based systems which deliver an average aerosol dose of between 30 and 50 micrograms per second. Only a small percentage of the total drug aerosol plume is effectively deposited in the lung. The drug efficacy is controlled by the drug aerosol particle size, with the optimum size being from 1-4 micrometers for deep penetration into the alveolar region within the lungs.
Existing aerosol drug delivery systems have the inherent problem of agglomeration for dry powders and coagulation for droplets. A substantial amount of the aerosolized drug forms larger particles that never reach the critical areas of the lungs. Existing delivery systems do not form monosize particles. Reagglomeration of the drug aerosols produces a broader than predicted particle distribution which, in turn, restricts particle dispersion and promotes variation of deposition pattern in the lungs.
Nebulizers have commonly been utilized for delivery of drugs to the pulmonary system. More recently, aerosolized delivery of genetic material to the pulmonary system has been proposed. U.S. Pat. No. 5,641,662 issued Jun. 24, 1997 to Debs et al discloses methods and compositions for producing a mammal capable of expressing an exogenously supplied gene in cells of the airway. Lipid carrier nucleic acid complexes are prepared and then delivered via aerosol to the lung airway. The methods and compositions are stated to be useful for in vivo gene therapy of pulmonary disorders.
U.S. Pat. No. 5,544,646 issued Aug. 13, 1996 to Lloyd et al and U.S. Pat. No. 5,660,166 issued Aug. 26, 1997 to Lloyd et al disclose systems for the intrapulmonary delivery of aerosolized aqueous formations. These patents describe delivery of an aerosolized drug through a porous membrane.
U.S. Pat. No. 5,278,626 issued Jan. 11, 1994 to Poole et al discloses a system for monitoring and analyzing impurities in a liquid by analyzing the non-volatile residue of droplets of the liquid. The system includes a droplet generator for generating a stream of droplets of the liquid, a droplet inspection unit, a drop-on-demand unit for removing selected droplets from the stream of droplets, a heat exchanger for drying the droplets to provide non-volatile residue particles and a particle size measurement unit.
When treating patients with high potency, toxic drug medications, such as peptides, insulin, oncology treatments, AIDS "cocktail" therapy, etc., or precious, expensive genetic materials, such as for cystic fibrosis, replication defective adenovirus gene therapy, liposome vector gene transfection therapy, cancer therapy etc., there is little margin for dose error due to improper particle size and/or improper dose concentration. Correct particle size and dose concentration are essential for effective lung to bloodstream absorption by the human body. Accordingly, there is a need for improved devices for delivery of drugs and genetic material to the pulmonary system.